The proposed research seeks to elucidate the relationship between nucleotide sequence organization of integrated feline retrovirus genes (FeLV, RD114) and biological expression of these proviruses in vivo and in vitro. Restriction enzyme site mapping of integrated FeLV-related sequences in DNA's of normal feline cells and in heterologous cells infected exogenously with FeLV show clearly that even those endogenous sequences which are full length contain considerable segments of non-homology with the exogenous virus, particularly at the 3' end of the molecule. Cloned isolates of endogenous sequences are uniformally non-infectious in transfection assay, whereas 4 of 14 isolates cloned from an FeLV infected human cell line (RD) were competent for virus production in the same assay. All 14 isolates are identical in sequence arrangement by restriction site mapping and no areas of mismatch are detected in S1 nuclease treated heteroduplexes. Continuing studies will examine the integration and expression of both infectious and non-infectious FeLV provirus clones in a tk- cell line from which transformants can be selected following cotransformation.